1. Field of the Invention
The present invention relates to a novel crystalline form, hereinafter referred to as crystalline Form II, of 7-chloro-N,N,5-trimethyl-4-oxo-3-phenyl-3,5-dihydro-4H-pyridazino[4,5-b]indole-1-acetamide.
This invention also relates to processes for the preparation of such crystalline form, and to methods of use thereof for the prevention and treatment of diseases related to peripheral-type benzodiazepine receptors.
2. Description of the Art
7-Chloro-N,N,5-trimethyl-4-oxo-3-phenyl-3,5-dihydro-4H-pyridazino[4,5-b]indole-1-acetamide, which has the structure of Formula (A):
possesses a high affinity for the peripheral-type benzodiazepine receptors. The preparation, physical properties and beneficial pharmacological properties of 7-chloro-N,N,5-trimethyl-4-oxo-3-phenyl-3,5-dihydro-4H-pyridazino[4,5-b]indole-1-acetamide are described in, for example, U.S. Pat. No. 6,262,045 and, in particular, U.S. Pat. No. 6,395,729, both of which are incorporated by reference in their entirety. The processes described in these patents result in the isolation of 7-chloro-N,N,5-trimethyl-4-oxo-3-phenyl-3,5-dihydro-4H-pyridazino[4,5-b]indole-1-acetamide in one defined crystalline form, herein designated as Form I.
The limited solubility of crystalline Form I of 7-chloro-N,N,5-trimethyl-4-oxo-3-phenyl-3,5-dihydro-4H-pyridazino[4,5-b]indole-1-acetamide in both aqueous solutions (generally less than 0.01 mg/ml) and non-aqueous formulation solvents (generally less than 3 mg/ml) presents difficulties in the administration and storage of formulations containing this compound. Preliminary studies carried out with standard formulations have led to limited absorption of the drug. Therefore, there is a need for new solid forms of 7-chloro-N,N,5-trimethyl-4-oxo-3-phenyl-3,5-dihydro-4H-pyridazino[4,5-b]indole-1-acetamide and new methods of their preparation.